BioProject

Introduction: Myotonic dystrophy of type 1 (DM1), the most common dystrophy in adults, is an autosomal dominant inherited disease, affecting around 1 in 8000 person. More...

Introduction: Myotonic dystrophy of type 1 (DM1), the most common dystrophy in adults, is an autosomal dominant inherited disease, affecting around 1 in 8000 person. Patients suffering from DM1 develop essentially muscle disorders such as myotonia, muscle weakness, muscle loss and atrophy. The disease is caused by the mutation of the DMPK "Dystrophia Myotonica Protein Kinase" gene. The mutation correspond to an abnormally large expansion of CTG tri-nucleotides repeats located in the 3'-untranslated region of this gene. Expanded CTG repeats are normally transcribed, but accumulates in RNA aggregates that sequester RNA-binding proteins such as the splicing regulator MBNL1. Consequently, due to MBNL1 sequestration, DM1 is characterized by aberrant splicing of a wide number of mRNA, which are themselves responsible for the symptoms observed in the disease. Purpose: To determine as much as possible novel splicing misregulations taking place in DM1 skeletal muscle, we performed a paired-end RNA sequencing (RNA-seq) using muscles samples of normal individuals (CTRL, n=3) versus muscles of DM1 patients (DM1, n=3). The data was analyzed by a bioinformatical software, called MISO, in order to map the alternative splicing changes between normal and DM1 muscle. The aim of this study was to get a broad and precise view of the splicing changes occurring in DM1 muscle. Overall design: PolyA RNA extracted from skeletal muscle biopsies originating from normal individuals (CTRL, n=3) or patients suffering of myotonic dystrophy type I (DM1, n=3), were analyzed by massive paired-end RNA sequencing. Less...